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微小RNA-195通过直接靶向肝癌衍生生长因子来抑制宫颈癌肿瘤的行为。

MicroRNA-195 inhibits the behavior of cervical cancer tumors by directly targeting HDGF.

作者信息

Song Rongrong, Cong Lin, Ni Guantai, Chen Min, Sun Honmei, Sun Yunxia, Chen Meiling

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

Prenatal Diagnosis Center, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

出版信息

Oncol Lett. 2017 Jul;14(1):767-775. doi: 10.3892/ol.2017.6210. Epub 2017 May 19.

Abstract

MicroRNAs (miRNAs/miRs) are a class of conserved non-coding endogenous small regulatory RNAs that regulate target gene expression by binding to the 3'-untranslated region of target mRNAs in a base-pairing manner, resulting in repression of transcription or degradation of target mRNAs. It has been demonstrated previously that the abnormal expression of miRNAs is involved in the carcinogenesis and progression of cervical cancer. The aim of the present study was to investigate the expression, biological functions and underlying molecular mechanisms of miR-195 in cervical cancer. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of miR-195 in cervical cancer tissues and cell lines. Following transfection, an MTT assay, cell migration and invasion assays, western blot analysis and a dual-luciferase reporter assay were performed in human cervical cancer cells. In the present study, it was identified that miR-195 was downregulated in cervical cancer tissues and cell lines. Additionally, upregulation of miR-195 and knockdown of hepatoma-derived growth factor (HDGF) inhibited proliferation, migration and invasion of cervical cancer cells. Furthermore, a dual-luciferase reporter assay identified that HDGF was a direct target gene of miR-195. RT-qPCR and western blot analysis demonstrated that miR-195 mimic inhibited HDGF expression at the mRNA and protein levels, whereas miR-195 inhibitor enhanced HDGF expression at the mRNA and protein levels. These results indicated that miR-195 targeted HDGF to inhibit the behavior of tumors in cervical cancer. These results also suggested that miR-195 was a potential therapeutic biomarker of cervical cancer.

摘要

微小RNA(miRNA/miR)是一类保守的非编码内源性小调节RNA,通过与靶mRNA的3'-非翻译区以碱基配对方式结合来调节靶基因表达,从而导致转录抑制或靶mRNA降解。先前已证明miRNA的异常表达与宫颈癌的发生和进展有关。本研究的目的是探讨miR-195在宫颈癌中的表达、生物学功能及潜在分子机制。采用逆转录定量聚合酶链反应(RT-qPCR)检测miR-195在宫颈癌组织和细胞系中的表达水平。转染后,对人宫颈癌细胞进行MTT试验、细胞迁移和侵袭试验、蛋白质印迹分析及双荧光素酶报告基因试验。在本研究中,发现miR-195在宫颈癌组织和细胞系中表达下调。此外,miR-195的上调和肝癌衍生生长因子(HDGF)的敲低抑制了宫颈癌细胞的增殖、迁移和侵袭。此外,双荧光素酶报告基因试验确定HDGF是miR-195的直接靶基因。RT-qPCR和蛋白质印迹分析表明,miR-195模拟物在mRNA和蛋白质水平上抑制HDGF表达,而miR-195抑制剂在mRNA和蛋白质水平上增强HDGF表达。这些结果表明,miR-195靶向HDGF以抑制宫颈癌中的肿瘤行为。这些结果还表明,miR-195是宫颈癌潜在的治疗生物标志物。

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